6-Hydroxydopamine is a neurotoxin which has recently been shown in our Branch to be produced in very small amounts endogenously in normal rat brain. This neurotoxin is probably produced as a by-product of dopamine degradation. Since motor hyperexcitation is a infrequent manifestation of psychotic states, the question has been raised as to whether physical hyperactivity may increase brain dopamine and consequently brain 6-hydroxydopamine and thereby contribute to the brain dysfunction frequently seen in schizophrenia. In an attempt to answer this question, a rat model of physical stress by forced wheel running is being developed. The model would involved forced wheel running of Brown Norway rats to the point of exhaustion. Recovery would be monitored by open field behaviors. Biochemical studies involving dopamine, its metabolites (including 6-hydroxydopamine), and other neurochemicals would help delineate the role of physical hyperactivity and concomitant stress on brain function. The model is currently in the planning phase.
